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This study aimed to characterize the single\u2010dose pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) \u226590\u00a0ml\/min; <jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>20), severe <jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> (CrCl &lt;30\u00a0ml\/min; <jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>14), or end\u2010stage renal disease requiring haemodialysis (<jats:styled-content style=\"fixed-case\">ESRD<\/jats:styled-content>;<jats:italic> n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>7). <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> and adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) were assessed after a single 3\u00a0mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe <jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ESRD<\/jats:styled-content> patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre\u2010 and post\u2010dialyser samples collected from <jats:styled-content style=\"fixed-case\">ESRD<\/jats:styled-content> patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s was generally similar across groups, but grade 3 and 4 <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s were more frequent in the severe <jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ESRD<\/jats:styled-content> groups versus the normal group (79%\/57% vs. 45%), as were serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s (43%\/43% vs. 15%). The <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> and safety results support a reduced ixazomib dose of 3\u00a0mg in patients with severe <jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ESRD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.14125","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T04:00:47Z","timestamp":1463716847000},"page":"748-759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["A pharmacokinetics and safety phase 1\/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end\u2010stage renal disease requiring haemodialysis"],"prefix":"10.1111","volume":"174","author":[{"given":"Neeraj","family":"Gupta","sequence":"first","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Donald","family":"Harvey","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Badros","sequence":"additional","affiliation":[{"name":"University of Maryland Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brea","family":"Lipe","sequence":"additional","affiliation":[{"name":"University of Kansas Clinical Research Center Fairway KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Kukreti","sequence":"additional","affiliation":[{"name":"University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Berdeja","sequence":"additional","affiliation":[{"name":"Sarah Cannon Cancer Center Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010Min","family":"Hui","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Qian","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajai","family":"Chari","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2014.71"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.29"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0288"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0498"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007309563"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(99)90014-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.607"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2232"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2009.n.059"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.8791"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404284"},{"key":"e_1_2_8_14_1","unstructured":"EMEA. 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